Heterogeneity in Alzheimer’s Disease: an Exercise in the Resolution of a Phenotype

  • M. F. Folstein
  • A. Warren
  • P. R. McHugh
Part of the Research and Perspectives in Alzheimer’s Disease book series (ALZHEIMER)

Summary

Clinical features related to age of onset, including amnesia, aphasia, apraxia, agnosia, depression, and fingerprint and platelet abnormalities, suggest heterogeneity in Alzheimer’s disease. Since some of these features run in Alzheimer’s disease families there could be genetic heterogeneity. Understanding the mechanisms which determine the age of onset and related features will be as important as the discovery of the genes, because delay of the age of onset could push it beyond the normal life span and thus eliminate expression of Alzheimer’s disease in human populations even though the genes themselves and their possible beneficial effects would remain.

Knowledge of potential heterogeneity will aid in the design of linkage studies. Criteria must be constructed for the purpose of identifying probands and secondary cases in linkage studies in order to reduce the number of false positives. To put it another way, we must increase the predictive value of case detection methods, particularly regarding early cases, in linkage studies.

Keywords

Depression Dementia Phenyl Ketone Neurol 

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References

  1. Alzheimer A (1907) Über eine eigenartige Erkrankung der Hirnrinde. Allgemeine Zeitschrift für Psychiatris und Psychisch-Gerichtliche Medicin 64: 146–148Google Scholar
  2. Appell J, Kertesz A, Fisman M (1982) A study of language functioning in Alzheimer patients. Brain Lang 17: 73–91PubMedCrossRefGoogle Scholar
  3. Berg L, Danziger WL, Storandt M, et al. (1984) Predictive features in mild senile dementia of the Alzheimer type. Neurology 34: 563–569PubMedGoogle Scholar
  4. Bondareef W, Mountjoy OQ, Roth M (1981) Selective loss of neurons of origin of adrenergic projection to cerebral cortex (nucleus locus ceruleus) in senile dementia. Lancet I: 783–784CrossRefGoogle Scholar
  5. Breitner JCS, Folstein MF (1984) Familial Alzheimer’s disease: a prevalent disorder with specific clinical features. Psychol Med 14: 63–80PubMedCrossRefGoogle Scholar
  6. Breitner JC, Silverman JM, Mohs RC, Davis KL (1988) Familial aggregation in Alzheimer’s disease: comparison of risk among relatives in successive generations. Neurology 38: 207–212PubMedGoogle Scholar
  7. Chui HC, Teng EL, Henderson VW, Moy AC (1985) Clinical subtypes of dementia of the Alzheimer type. Neurology 35: 1544–1550PubMedGoogle Scholar
  8. Constantinidis J (1978) Is Alzheimer’s disease a major form of senile dementia? Clinical, anatomical, and genetic data. In: Katzman R, Terry RD, Bick KL (eds) Alzheimer’s disease: senile dementia and related disorders (Aging, vol 7). Raven Press, New York, pp 15–25Google Scholar
  9. Constantinidis J, Garrone G, Tissot R, DeAjuriaguerra J (1965) L’incidence familiale des alterations neurofibrillaires corticales d’Alzheimer. Psychiat Neurol (Basel) 51: 330–344Google Scholar
  10. Dalton AJ, Crapper DR (1984) Influence of memory deterioration in aging persons with Down’s Syndrome. In: Berg JM (ed) Perspectives and progress in mental retardation. Biomedical aspects, vol 2. University Park Press, Baltimore, pp 55–62Google Scholar
  11. Eisner D (1983) Downs syndrome and aging: Is senile dementia inevitable? Psychol Rep 52:119–124PubMedCrossRefGoogle Scholar
  12. Faber-Langendoen K, Morris JC, Knesevich JW, LaBarge E, Miller JP, Berg L (1988) Aphasia in senile dementia of the Alzheimer type. Ann Neurol 23: 365–370PubMedCrossRefGoogle Scholar
  13. Fitch N, Becker R, Heller A (1988) The inheritance of Alzheimer’s disease: or new interpretation. Ann Neurol 23: 14–19PubMedCrossRefGoogle Scholar
  14. Folstein MF, Breitner J (1981) Language disorder predicts familial Alzheimer’s disease. Johns Hopkins Med J 21: 686–689Google Scholar
  15. Foster NL, VanDerSpek AF, Aldrich MS, Berent S, Hichwa RH, Sackellares JC, Gilman S, Agranoff BW (1987) The effect of diazepam sedation on cerebral glucose metabolism in Alzheimer’s disease as measured using positron emission tomography. J Cereb Blood Flow Metab 7: 415–420PubMedCrossRefGoogle Scholar
  16. Go RCP, Todorov AB, Elston RC, Constantinidis J (1979) The malignancy of dementias. Ann Neurol 3: 559–561CrossRefGoogle Scholar
  17. Haxby JV, Grady CL, Duara R, Schlalageter N, Berg G, Rapoport SI (1987) Neocortical metabolic abnormalities precede nonmemory cognitive defects in early Alzheimer-type. Arch Neurol 43: 882–885Google Scholar
  18. Huff FJ, Auerbach J, Charavarti A, Boller F (1988) Risk of dementia in relatives of patients with Alzheimer’s disease. Neurology 38: 786–790PubMedGoogle Scholar
  19. Jagust WJ, Budinger TF, Reed BR (1987) The diagnosis of dementia with single photon emission computed tomography. Arch Neurol 44: 258–263PubMedGoogle Scholar
  20. Jervis G A (1948) Early senile dementia in mongoloid idiocy. Am J Psychiatry 105: 102–106PubMedGoogle Scholar
  21. Johnson KA, Mueller ST, Walshe TM, English RJ, Holman BL (1987) Cerebral perfusion imaging in Alzheimer’s disease. Use of single photon emission computed tomography and iofetamine hydrochloride 1123. Arch Neurol 44: 165–168PubMedGoogle Scholar
  22. Katzman R, Terry R, DeTeresa R, Brown T, Davies P, Fuld P, Renbing X, Peck A (1988) Clinical, pathological and neurochemical changes in dementia: a subgroup with preserved mental status and numerous cortical plaques. Ann Neurol 23: 138–144PubMedCrossRefGoogle Scholar
  23. Larsson T, Sjogren T, Jacobson G (1963) Senile dementia. Acta Psych Scand (Copenh) [Suppl 167] 39: 1–259Google Scholar
  24. Malamud N (1972) Neuropathology of organic brain syndromes associated with ageism. In: Gaitz CM (ed) Aging and the brain. New York, Plenum, pp 63–87Google Scholar
  25. Martin RL, Gerteis G, Gabrielli WF (1987) A family-genetic study of dementia of Alzheimer type.Google Scholar
  26. Mohs RC, Breitner JC, Silverman JM, Davis KL (1987) Alzheimer’s disease. Morbid risk among first-degree relatives approximates 50% by 90 years of age. Arch Gen Psychiatry 44: 405–408PubMedGoogle Scholar
  27. Nee LE (1987) Fingerprint patterns in subjects at risk for inherited Alzheimer’s disease. International Symposium of Familial Alzheimer’s Disease, Tulsa, Oklahoma 1987Google Scholar
  28. Powell D, Folstein MF (1984) Pedigree study of familial Alzheimer’s disease. J Neurogenetics 1: 189–197CrossRefGoogle Scholar
  29. Prichard JC (1837) A treatise on insanity and other disorders affecting the mind. Haswell, Barnington and Haswell, Philadelphia, pp 69–80Google Scholar
  30. Rovner BW, Broadhead J, Spencer M, Carson K, Folstein MF (1988) Depression and Alzheimer’s disease. Am J Psychiatry (in press)Google Scholar
  31. Seltzer B, Sherwin I (1983) A comparison of clinical features in early-and late-onset primary degenerative dementia: one entity or two? Arch Neurol 40: 143–146PubMedGoogle Scholar
  32. Seltzer B, Sherwin I (1986) Fingerprint pattern differences in early-and late-onset primary degenerative dementia. Arch Neurol 43: 665–668PubMedGoogle Scholar
  33. Weinreb HJ (1985) Fingerprint patterns in Alzheimer’s disease. Arch Neurol 42: 50–54PubMedGoogle Scholar
  34. Wisniewski KE, Wisniewski HM, Wen GY (1985) Occurrence of neuropathological changes in dementia of Alzheimer’s disease in Down’s syndrome. Ann Neurol 17: 278–282PubMedCrossRefGoogle Scholar
  35. Zweig RM, Ross CA, Hedreen JC, Steele C, Cardillo JE, Whitehouse PJ, Folstein MF (1988) The neuropathology of aminergic nuclei. Ann Neurol 24: 233–242PubMedCrossRefGoogle Scholar
  36. Zubenko GS, Wusylko M, Cohen BM, Boiler F, Teply I (1987) Platelet membraned fluidity in Alzheimer’s disease. Science 238: 539–542PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1988

Authors and Affiliations

  • M. F. Folstein
  • A. Warren
  • P. R. McHugh

There are no affiliations available

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